Endometriosis is an estrogen-dependent, inflammatory disease affecting approximately 176 million women worldwide. It occurs when cells from the lining of the uterus grow in other areas of the body. It usually leads to pain, irregular bleeding, and infertility.
It has been reported that immune dysregulation may play a role in endometriosis (Rier and Yeaman 1997). For instance, animal modeling studies have indicated that lymph node immune cell populations including T cells, dendritic cells and B cells were increased and endometrial stromal cells were significantly increased in lymph nodes from animals with induced endometriosis (Hey-Cunningham, Fazleabas et al. 2011).
In addition, it has been documented that cytokines may play a critical role in immune cell differentiation, growth and functions (St Georgiev and Albright 1993; Bryant, Ma et al. 2007; Steppich, Moog et al. 2007). Alterations in cytokine expression associated with inflammation have long been observed in individuals with immune-mediated diseases (Feng, Scheinberg et al. 2012; Hu and Hwang 2012). Cytokines may be dysregulated in patients with endometriosis (Hou, Sun et al. 2009), suggesting that cytokines may play a role in endometriosis.
Epigenetic events are crucial in the control of both normal cellular processes and abnormal events associated with cancer (Feinberg, Ohlsson et al. 2006) and other human diseases (Egger, Liang et al. 2004). Major epigenetic mechanisms include DNA methylation, covalent post-translational modifications of histone proteins, and RNA-mediated gene silencing such as via small interfering RNA (siRNA) and microRNA (miRNA). It has been reported that miRNAs, small noncoding RNAs that regulate gene expression by binding to complementary target mRNAs and inhibiting their translation, have been shown to play a crucial role in the regulation of cytokine genes (O'Connell, Kahn et al.; Xiao and Rajewsky 2009), and are involved in the production and functions of immune cells. The specific role of some individual miRNAs has been demonstrated in hematopoiesis and immune cell regulation. For example, miR-223 is involved in human granulopoiesis, erythropoiesis and B cell differentiation (Malumbres and Lassos 2010), miR-155 promotes Th2 cell differentiation (Rodriguez, Vigorito et al. 2007), and miR-326 promotes Th17 cell development (Du, Liu et al. 2009).
miRNAs have also been implicated in immune regulation. For example, miR-146a regulates the immune response to bacterial infections and miR-181a modulates the sensitivity of T lymphocytes to antigens by regulating expression levels of various phosphatases from the T-cell receptor signaling (Anglicheau, Muthukumar et al. 2010).
Recent studies indicate that microRNAs may play a role in endometriosis (Hawkins, Creighton et al. 2011; Wang, Zhao et al. 2013). Elucidation of roles of specific microRNA dysregulated in endometrial patients could have great implications in understanding the pathogenesis of endometriosis and developing diagnostic markers and therapeutic targets for endometriosis.
What are needed in the art are treatment methods for endometriosis that include early detection of the disease state.